Abstract
Purpose: To evaluate left ventricular function prospectively and comparatively to healthy controls and prospectively short term on standard treatment in patients with thyroid dysfunction function.
Material and methods: We investigated 39 patients with hyperthyroidism, 24 patients with hypothyroidism and 40 controls by echocardiography and systolic time intervals (STI) at beginning of treatment and six weeks later after initiation of treatment. Heart rate (HR), pre-ejection period (PEP) and its corrected value PEPc, ejection time (ET) and its corrected value (ETc) and PEP/ET ratio were studied. End-diastolic, end-systolic dimensions (EDD, ESD), shortening fraction (SF), mean velocity of circumferential fiber shortening (MVCFS), systemic vascular resistance (SVR) and left ventricular mass index (LVMi) were examined.
Results: STI in hyperthyroidism were significant different: HR was increased, ET, ETc, PEP, PEPc and PEP/ET was decreased. CI was greater, MVCFS was greater and SF was higher, SVR was decreased and LVMi was greater. In follow-up treatment significant recovery in HR, PEP, ET and ETc and MVCFS was found . STI in hypothyroid patients were significant changed: PEP and PEP/ET were increased . CI was lower and SVR was higher, MVCFS was decreased and LVMi was greater, SF and ESD were changed too. When on standard hormone replacement treatment for 6 weeks no changes in indices studied were found. High correlations were seen when plotting thyroxin hormone levels against MVCFS and between MVCFS and SVR.
Materials and Methods
Patients included in the study were: i) a group of 39 patients with newly diagnosed or relapsed and untreated diffuse or multinodular goiter with clinical and biochemical evidence of increased secretion of thyroid hormones; ii) a second group of 24 patients with autoimmune, idiopathic, postoperative or drug induced hypothyroidism with clinical and biochemical evidence of decreased secretion of thyroid hormones and iii) control group of 40 healthy volunteers without a history, clinical, radiographic, electrocardiographic, echoca rdiographic evidence of cardiovascular disease. Inclusion for both groups of patients with thyroid dysfunction were normal blood pressure, normal renal function - blood urea nitrogen and creatinine and normal hemoglobin.
According to the recommendations of AAE M-mode echocardiographic indices were as follows: endsystolic (ESD), end-diastolic dimensions (EDD), interventricular septum thickness (IVST) and posterior left ventricular wall thickness (PLVWT) in mm, shortening fraction in %, ejection fraction in %, mean circumferential fibre shortening (MCFS)-fractional shortening/left ventricular ejection time in circ/s, left ventricular mass index (LVMi) in g/m2 and cardiac index( CI) l/min/m2 , systemic vascular resistance (SVR) - (80 ? MAP(mean arterial pressure)/CO) in ???/s/l. (4) Systolic time intervals with the addition of phonocardiography and carotis sphigmography were also investigated as follows and were corrected for heart rate: ejection time (ETc), preejection time interval PET and the ration PEP/ET. (1,2,3) Laboratory investigations included: Triiodothyronine hormone (T3) – reference limits 1.2 - 3.5 nmol/ l and thyroxin (T4)- reference limits 50 to 155 nmol/ l by radio-immunoassay and protein bound iodine / PBI /- normal reference limits 4-8 mg%. Non-invasive tests were performed at the start of treatment and 6 consecutive weeks afterwards after initiation of treatment.
Results
Hyperthyroid patients compared to control group
Systolic time intervals: Patients with hyperthyroidism compared to control group were identified to have the following statistically significant differences: heart rate was increased, ejection time / corrected value and pre-ejection period and its corrected value were all shorter, and PEP/ET was decreased (p< 0.001) .Echocardiography: examination of both groups revealed statistically significant differences in the following parameters: the cardiac index was greater (p< 0.001), MVCFS was greater with p < 0.02 and shortening fraction was higher ( p <0. 05), total peripheral resistance was decreased and left ventricular mass index was greater (r < 0.01) (Table 1)
Hypothyroid patients compared to control group
Systolic time intervals: Patients with hypothyroidism compared to control group were identified by following statistically significant differences: pre-ejection period and PEP/ET were increased ( p < 0.01) In echocardiography cardiac index was lower and total peripheral resistance was higher (?<0 .001), MCFS was decreased and left ventricular mass index was greater ( ? < 0 .01), shortening fraction, ejection fraction and end systolic diameter were changed too (?<0 .02 ( Table 1)
Six-weeks follow-up of patients with hyper and hypothyroidism on standard treatment
For patient with hyperthyroidism on standard treatment followed-up for 6 weeks the significant changes were: for heart rate and PEP (p < 0.01) and ET and ETc ( p < 0.02) and MVCFS (p<0.05). For patients with hypothyroidism 6-weeks of dynamic monitoring during standard hormone replacement treatment did not lead to statistical changes in indices studied. (Table 2)
Additional echocardiographic findings
a. mitral valve prolapse - in 10% (4) patients with hyperthyroidism mitral valve prolapse was found.
b. asymmetric septal hypertrophy - in 8% (2) patients with a severe long-term hypothyroidism asymmetric septal hypertrophy with an index of septal asymmetry of more than 2.4 and hypertrophic subaortic stenosis with systolic anterior motion of the anterior mitral leaflet.was found.
c. pericardial effusion - in 50% (12) patients with long-lasting and severe hypothyroidism small (up to300 ml) pericardial effusion was found.
Correlations of hemodynamic variables and thyroid hormones
High correlations were found when plotting thyroxin levels against mean velocity of circumferential fiber shortening (MVCFS) of a joint group of hyperthyroid and hypothyroid patients (r= + 0.75) and between against mean velocity of circumferential fiber shortening (MVCFS) and total peripheral resistance (r= -0.45) of a group of controls and patients with hyper- and hypothyroidism.
Discussion
The cardiovascular echocardiographic indices and systolic time intervals of two groups of patients with thyroid involvement and clinical and biochemical signs and symptoms of deranged thyroid hormone secretion with various underlying etiologies were studied only on the basis of thyroid hormone status. The average age of both groups of patients (40 years in the group with hyperthyroidism and 44 in the group with hypothyroidism) is most commonly found in the literature. There was a change in heart rate and systolic time intervals which were partially reverse on the six-week of follow-up treatment. Echocardiographic parameters cardiac index, total peripheral resistance and left ventricular mass index were also changed. Contractility parameters shortening fraction and mean velocity of circumferential fiber shortening were also increased and MVCFS underwent some normalization on a six week follow-up period. There were changes in PEP, which did not undergo some partial, but statistical significant reversal on the six week of follow-up. Cardiac output, peripheral resistance and left ventricular mass index were also changed, as were indices of cardiac and myocardial performance shortening fraction mean velocity of circumferential fiber shortening were decreased but did not go significant change on the six week of replacement hormonal therapy.
The mechanism of hyper-dynamic high-output state of the cardiovascular system in hyperthyroidism is characterized by a significant increase in cardiac index secondary to increased heart rate, unchanged stroke volume and ejection fraction with no significant change in mean arterial pressure but at the expense of significantly reduced peripheral vascular resistance achieved by high speed ejection with shortened systolic time intervals and shorter and quicker diastolic filling. The above data do not speak in favor of an increased contractility of left ventricular myocardium under the influence solely of thyroid hormones.
When analyzing the potential factors influencing cardiac function in hyperthyroidism they include reduced peripheral resistance, increased contractility, increased blood volume, increased heart rate. (5-12)
The mechanisms of hypo-dynamic low-output state of the cardiovascular system in hypothyroidism are characterized by a significant reduction in cardiac index, unchanged heart rate at the expense of reduced stroke volume and ejection fraction with a significant change in mean arterial pressure and a significant increase in total peripheral resistance. And increased total peripheral resistance plays a major role in reduction of contractile indices of the left ventricle-fractional shortening and mean velocity of circumferential fiber shortening. The decrease in cardiac output is reached at the expense of increased end-systolic dimension and by reducing the speed of ejection with increased systolic time intervals and prolongation of the time of diastolic filling. (13-17, 18-22)
References
1. Antani JA, Wayne HH, Kuzman WJ; Ejection phase indexes by invasive and noninvasive methods: An apexcardiographic, echocardiogrophic and ventriculographic correlative study. Am J Cardiol 43:239-246, 1979
2. Weissler AM, Lewis RP, Leighton RF; The systolic time intervals as a measure of the left ventricular performance in man. In: Yu PN, Goodwin JF, eds. Progress in Cardiology 1. Philadelphia: Lea & Febiger: 155-83, 1972.
3. Werf HG; Mechanocardiografic assessment of left ventricular function in coronary artery desease. Br Heart J 1980, 43:184 – 190,
4. Sahn DJ, DeMaria A, Kisslo J, Wewman A; Recommendations regarding quontitation in M-mode echocardiography of a survey of echocardiographic measurements. Circulation 1978 58/6:1072, .
5. Abrahansen AM, Haatgstaad, Oulie C; Haemodynamic studies of thyrotoxicosis before and after treatment. Acta Med Scand, 174:463, 1963.
6. Bush J, Waldorf S, Hansen PB, Rasumusen OO; Non-invasive measuring of circulatory effect of afterload reduction. Br. Heart J 1983 50/2:170-175, .
7. BlondeL, Skelton CL; Hyperthyroidism and cardiovascular disease. Cardiovasc Med 3/11:1145-1162, 1978.
8. Cohen MV, Schulman IC, Spenillo A, Surks MI; Effects of thyroid hormone on left ventricular function in patients treated for thyrotoxicosis. Am J Cardiol 48:33, 1981.
9. Friedman MJ, Okada RD, Ewy GAM, Hellman DJ; Left ventricular systolic and diastolic function in hyperthyroidism. Am Heart J 1982 104/6:1303, .
10. Lewis BS, Ehrenfeld EN, Lewis N, Gotsman MS; Echocardiographic LV function in thyrotoxicosis. Am Heart J 1979 97/4:460,
11. Merillon JP, Rassa PH, Chaster J et al; Left ventricular function and hyperthyroidism. Br Heart J 46:137-143, 1981
12. Shafer RB, Bianco JA; Assessment of cardiac reserve in patients with hyperthyroidism. Chest 78/2:269, 1980.
13. Limanova Z, Hradez J; The advantage of the use of echocardiographic evaluation in hypothyroid patients. Endocrinologie 75/2:187-196, 1980.
14. Bough EW, Crowley WF, Ridjway EC; Myocardial function in hypothyroidism. Arch Intern Med 1978. 138:1476,
15. Plotnick GD, Vassar DL, Parisi AF et al; Systolic time intervals in hypothyroidism. Am J Med Sci 277/3:263-268, 1979.
16. Santos AD, Miller PR, Mathew PK et al; Echocardiographic characterization of the reversible cardiomyopathy of hypothyroidism. Am J Med 68:675, 1980.
17. Utiger RD: Hypothyroidism, in Endocrinology, JL De Croot et al, eds New York Grune & Stratton: 471-488, 1979.
18. Feldman T, Borow KM, Sarne DH, Neumann A, Lang RM Myocardial mechanics in hyperthyroidism: importance of left ventricular loading conditions, heart rate and contractile state. J Am Coll Cardiol 1986 7:967–974
19. Kahaly GJ, Wagner S, Nieswandt J, Mohr-Kahaly S, Ryan TJ Stress echocardiography in hyperthyroidism. J Clin Endocrinol Metab 1999, 84:2308–2313
20. Bengel FM, Nekolla SG, Ibrahim T, Weniger C, Ziegler SI, Schwaiger M Effect of thyroid hormones on cardiac function, geometry, and oxidative metabolism assessed noninvasively by positron emission tomography and magnetic resonance imaging. J Clin Endocrinol Metab 2000, 85:1822–1827
21. Fadel BM, Ellahham S, Ringel MD, Lindsay J, Wartofsky L, Burman KD Hyperthyroid heart disease. Clin Cardiol 2000, 23:402–408
22. Toft AD, Boon NAThyroid disease and the heart. Heart 84:455–460 Klein I, Ojamaa K Thyrotoxicosis and the heart. Endocrinol Metab Clin North Am 2000 27:51–62
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